Key considerations for optimization of formulation and melt-extrusion process parameters for developing thermosensitive compound

Abstract

The melt-extrusion process is currently applied in the pharmaceutical field in the manufacturing of a variety of dosage forms and formulations, including solid dispersions. Though this technology is considered efficient and continuous, there are potential challenges of which, additional thermal degradation of drug substance because heat stress and shear forces are of a primary concern. This paper attempts to understand the impact of thermal and/or mechanical components of the melt-extrusion process on the stability of a thermosensitive drug substance during scale-up. The overall degradation profile of the drug substance was correlated with the various physical changes made to the extruder as well as the process temperature. The results suggested that the degradation profile of a thermosensitive drug substance could be controlled by proper design of screw assemblies and by optimization of screw rotations per minute, process temperature, and feed rate during development and scale-up.

Keywords::

• Melt extrusion
• extrusion temperature
• glass transition temperature
• thermosensitive compound
• twin-screw extruder

Acknowledgements

The work was carried out within the framework of a research project at Novartis Pharmaceuticals. The authors would like to thank James Kowalski for his contribution during the process scale-up and Jay Laskhman for his valuable suggestion. The authors also acknowledge Julie Cheng, Dolly Sehgal, Thomas Eske, Bianca Schwind, and Yanging Jang for their support with HPLC support. Finally the author would also like to thank Marilyn Alvine for initial MDSC/XRD support.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.